Role of corneal collagen cross-linking in bullous keratopathy: A systematic review

Corneal cross-linking (CXL), a corneal strengthening procedure, is known to alter anterior stroma swelling behavior and is one of the treatment modalities of bullous keratopathy (BK). There are multiple studies published on the role of CXL in the treatment of BK. These articles had heterogeneous study population, different protocols used, and variable conclusions. This systematic review aimed to determine the role of CXL in the treatment of BK. The primary outcomes considered were changes in central corneal thickness (CCT) after 1, 3, and 6 months of CXL. The secondary outcome measures were changes in visual acuity, corneal clarity, subjective symptoms, and complications after CXL. We included randomized control trials (RCTs), observational and interventional studies, and case series with reports of more than 10 cases in this review. In RCTs, the mean pre-CXL CCT (794.0 ± 178.5 μm) in the intervention group (n = 37), decreased at 1 month (750.9 ± 154.3 μm) followed by a subsequent increase, but this difference was not significant during the 6-month follow-up (P- value 0.28, 0.82, and 0.82 at 1, 3, and 6 months, respectively). In noncomparative clinical studies (n = 188), the mean pre-CXL CCT (794.0 ± 178.5 μm) decreased at 1 month (710.9 ± 127.2 μm, P < 0.0001). Seven of the 11 articles included in the review reported no significant improvement in vision with CXL. The initial improvement in corneal clarity and clinical symptoms was not sustained. Current evidence suggests that CXL has short-term efficacy in the treatment of BK. More RCTs with high-quality evidence are needed.